We will test the hypothesis that alcohol physical dependence is caused by a change in physical properties of biomembranes. We have shown by electron paramagnetic resonance (EPR) that low concentrations of ethanol in vitro have a fluidizing effect on mouse cell membranes. Now we will examine the EPR spectra of membranes from mice chronically treated with ethanol to see whether the order parameter returns to normal, and whether the lipid composition has changed in a way that might account for tolerance and physical dependence. We will use our two animal models for physical dependence, administering the ethanol by inhalation or in a liquid diet. We have established quantitative dose relations and time course for both models.